It is well known that people with insulin resistance present less vasodilatation mediated by insulin and an altered endothelium dependent vasodilatation. Additionally, it has been described that insulin causes a physiologic vasodilatation in the skeletal muscle of healthy subjects, an effect that is blocked in insulin-resistance obesity. In our population, we find that obesity, hypercholesterolemia and diabetes are related with a flow-mediated vasodilatation reduction. The endothelial dysfunction is strongly related with the insulin resistance syndrome. At the same time, the endothelial dysfunction worsens the resistance to insulin, increases the vascular reactivity and predisposes to cardiovascular disease. It has been proposed that the vasodilator effect of the insulin is primarily due to a greater expression of mRNA for endothelial nitric oxide synthase (eNOS) due to a probable increase of the transcriptional rate. There are elements to support the fact that this activity is modulated by C-kinase protein (PKC). The inhibition of PKC increases the mRNA levels for eNOS. Prolonged incubation of endothelial cells with a selective inhibitor of the PKC beta isoform increase the mRNA levels of eNOS. This observation may have important clinical implications since the PKC activation in the vasculature of diabetic subjects in alteration of the vascular wall. The existing relationship between endothelial dysfunction and insulin resistance is dependent on multiple factors. Obesity generates an alteration of the endothelial function in the metabolically active capillary bed, altering the lipase lipoprotein (LPL) that is linked to the endothelium by glycosaminoglycans. The ultimate loss of these caused by aggressive factors such as smoking and oxygen free radicals, alters the endothelial function and also impairs the action of the LPL causing hypertriglyceridemia which is an insulin resistance factor. At the same time, the alteration of endothelial function in the capillary beds reduces the interstitial flow, carrying less insulin or delaying its delivery to the muscular tissue. Additionally, it has been proposed that there is less surface of endothelium functionally normal in the vessels that are irrigating the skeletal muscle. It has also been shown that hyperinsulinemia predicts the appearance of atherosclerosis and cardiovascular events, independently of other risk factors.